Obesity affects millions of people in the U.S. and worldwide, and this disease has enormous health and economic consequences for our society. Existing treatments show limited efficacy, can possess troubling side effects, and often require long-term therapy. Discovery of a new treatment for obesity would have a very considerable scientific and commercial value. One approach to pharmacotherapy for appetite suppression is the development of 5-HT2C receptor agonists, which was the focus of our Phase One work. In Phase Two, we propose to optimize and further develop these leads through a Structure-Activity Relationship (SAR) program of synthesis and biological evaluation. From this project we specifically aim to discover one or more indole analogs showing efficacy in our animal model for appetite suppression that is equal to or better than approved medications. Such leads will also display favorable drug-like properties. The long-term goal of this project is to discover a new, improved pharmaceutical agent for treatment of obesity that can be licensed and developed for ultimate market approval. 7. Project Narrative Obesity is a serious health problem in the Unites States, and the existing drugs to help people lose weight are often not effective and have side effects. We are carrying out research to discover and develop a new drug for obesity. If we are successful, doctors will have another option to help obese people with their weight problem.